Nature Reviews Drug Discovery 11, 52-68 (January 2012) | doi:10.1038/nrd3620

The pharmacological landscape and therapeutic potential of serine hydrolases

Daniel A. Bachovchin1 & Benjamin F. Cravatt1  About the authors


Serine hydrolases perform crucial roles in many biological processes, and several of these enzymes are targets of approved drugs for indications such as type 2 diabetes, Alzheimer's disease and infectious diseases. Despite this, most of the human serine hydrolases (of which there are more than 200) remain poorly characterized with respect to their physiological substrates and functions, and the vast majority lack selective, in vivo-active inhibitors. Here, we review the current state of pharmacology for mammalian serine hydrolases, including marketed drugs, compounds that are under clinical investigation and selective inhibitors emerging from academic probe development efforts. We also highlight recent methodological advances that have accelerated the rate of inhibitor discovery and optimization for serine hydrolases, which we anticipate will aid in their biological characterization and, in some cases, therapeutic validation.

Author affiliations

  1. The Skaggs Institute for Chemical Biology and Department of Chemical Physiology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, California 92037, USA.

Correspondence to: Benjamin F. Cravatt1 Email:

Published online 3 January 2012

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